rs3773814

Variant names:

• chr3-130996904-A-C
• rs3773814
• NM_001378687.1:c.2243+108A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-130996904-A-C
• chr3-130996904-A-G
• chr3-130996904-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378687.1(ATP2C1):​c.2243+108A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 813,968 control chromosomes in the GnomAD database, including 9,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1416 hom., cov: 33)
  • Exomes 𝑓: 0.15 (8218 hom.)
• Consequence: ATP2C1 NM_001378687.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 1 publications found

Genes affected

ATP2C1 (HGNC:13211): (ATPase secretory pathway Ca2+ transporting 1) The protein encoded by this gene belongs to the family of P-type cation transport ATPases. This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium ions. Defects in this gene cause Hailey-Hailey disease, an autosomal dominant disorder. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ATP2C1 Gene-Disease associations (from GenCC):

• Hailey-Hailey disease

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 3-130996904-A-C is Benign according to our data. Variant chr3-130996904-A-C is described in ClinVar as Benign. ClinVar VariationId is 1265320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378687.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	NM_001378687.1	MANE Select	c.2243+108A>C		intron	N/A	NP_001365616.1
	ATP2C1	NM_001378511.1		c.2345+108A>C		intron	N/A	NP_001365440.1
	ATP2C1	NM_001199180.2		c.2345+108A>C		intron	N/A	NP_001186109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP2C1	ENST00000510168.6	TSL:5 MANE Select	c.2243+108A>C		intron	N/A	ENSP00000427461.1
	ATP2C1	ENST00000359644.7	TSL:1	c.2243+108A>C		intron	N/A	ENSP00000352665.3
	ATP2C1	ENST00000422190.6	TSL:1	c.2243+108A>C		intron	N/A	ENSP00000402677.2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18368 AN: 152080 Hom.: 1417 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.148 AC: 98167 AN: 661770 Hom.: 8218 AF XY: 0.146 AC XY: 52202 AN XY: 357402

African (AFR) AF: 0.0272 AC: 482 AN: 17740

American (AMR) AF: 0.132 AC: 5384 AN: 40798

Ashkenazi Jewish (ASJ) AF: 0.0803 AC: 1659 AN: 20672

East Asian (EAS) AF: 0.115 AC: 4114 AN: 35806

South Asian (SAS) AF: 0.111 AC: 7489 AN: 67522

European-Finnish (FIN) AF: 0.225 AC: 10188 AN: 45356

Middle Eastern (MID) AF: 0.0612 AC: 256 AN: 4182

European-Non Finnish (NFE) AF: 0.162 AC: 64021 AN: 395530

Other (OTH) AF: 0.134 AC: 4574 AN: 34164

GnomAD4 genome AF: 0.121 AC: 18366 AN: 152198 Hom.: 1416 Cov.: 33 AF XY: 0.121 AC XY: 9017 AN XY: 74392

African (AFR) AF: 0.0284 AC: 1181 AN: 41560

American (AMR) AF: 0.130 AC: 1989 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3470

East Asian (EAS) AF: 0.111 AC: 575 AN: 5184

South Asian (SAS) AF: 0.112 AC: 538 AN: 4822

European-Finnish (FIN) AF: 0.216 AC: 2283 AN: 10580

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11157 AN: 67958

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.136 Hom.: 2059

Bravo AF: 0.110

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3773814; hg19: chr3-130715748;